Skip to main content

Advertisement

SpringerLink
Log in

Resveratrol Supplementation Gender Independently Improves Endothelial Reactivity and Suppresses Superoxide Production in Healthy Rats

  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Purpose

Resveratrol, a polyphenolic compound mainly abundant in red wines, has beneficial cardiovascular effects on various pathological conditions. However, at present, the effect of resveratrol on health promotion remains unclear. Therefore, in this study, we assessed whether long-term resveratrol supplementation changes endothelial function, vascular contractility, nitric oxide and superoxide production in healthy male and female rats.

Methods

Wistar rats were treated with resveratrol (50 mg/l) in their drinking water for 3 weeks. We investigated relaxation to acetylcholine (10−9−10−4 M) and contractions to phenylephrine (10−9−3 × 10−4 M) and angiotensin II (10−10−10−5 M) in either endothelium-intact or denuded aortae from control and resveratrol-treated male and female rats. Aortic superoxide production capacity was measured in response to provocation by angiotensin II and NAD(P)H. Plasma nitrite/nitrate levels and superoxide dismutase (SOD) activity were also evaluated.

Results

Resveratrol supplementation gender independently increased relaxation to acetylcholine and decreased contractions to phenylephrine and angiotensin II in endothelium-intact aortic rings, but not in endothelium-denuded arteries, from healthy male and female rats. This was associated with increased plasma nitrite/nitrate levels. Furthermore, resveratrol caused a refractoriness to angiotensin II and NAD(P)H-induced provocation in superoxide production.

Conclusion

Our results suggest that resveratrol supplementation gender independently could improve the capacity of endothelial function and suppression of oxidative stress under physiological conditions. Resveratrol ingestion indicates a potential for cardiovascular health promotion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. German JB, Walzem RL. The health benefits of wine. Annu Rev Nutr. 2000;20:561–93.

    Article  CAS  PubMed  Google Scholar 

  2. Sato M, Maulik N, Das DK. Cardioprotection with alcohol: role of both alcohol and polyphenolic antioxidants. Ann New York Acad Sci. 2002;957:122–35.

    Article  CAS  Google Scholar 

  3. Chen CK, Pace-Asciak CR. Vasorelaxing activity of resveratrol and quercetin in isolated rat aorta. Gen Pharmacol. 1996;27:363–6.

    CAS  PubMed  Google Scholar 

  4. Orallo F, Alvarez E, Camina M, Leiro JM, Gomez E, Fernandez P. The possible implication of trans-resveratrol in the cardioprotective effects of long-term moderate wine consumption. Mol Pharmacol. 2002;61:294–302.

    Article  CAS  PubMed  Google Scholar 

  5. Rakici O, Kiziltepe U, Coskun B, Aslamacı S, Akar F. Effects of resveratrol on vascular tone and endothelial function of human saphenous vein and internal mammary artery. Int J Cardiol. 2005;105:209–15.

    Article  PubMed  Google Scholar 

  6. Wallerath T, Deckert G, Ternes T, Anderson H, Li H, Witte K, et al. Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation. 2002;106:1652–8.

    Article  CAS  PubMed  Google Scholar 

  7. Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge CM. Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology. 2000;141:3657–67.

    Article  CAS  PubMed  Google Scholar 

  8. Klinge CM, Wickramasinghe NS, Ivanova MM, Dougherty SM. Resveratrol stimulates nitric oxide production by increasing estrogen receptor α-Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells. FASEB J. 2008;22:2185–97.

    Article  CAS  PubMed  Google Scholar 

  9. Chow S-E, Hshu Y-C, Wang J-S, Chen J-K. Resveratrol attenuates oxLDL-stimulated NADPH oxidase activity and protects endothelial cells from oxidative functional damages. J Appl Physiol. 2007;102:1520–7.

    Article  CAS  PubMed  Google Scholar 

  10. Soylemez S, Gurdal H, Sepici A, Akar F. The effect of long-term resveratrol treatment on relaxation to estrogen in aortae from male and female rats: role of nitric oxide and superoxide. Vasc Pharmacol. 2008;49:97–105.

    Article  CAS  Google Scholar 

  11. Zou J-G, Wang Z-R, Huang Y-Z, Cao K-J, Wu JM. Effect of red wine and wine polyphenol resveratrol on endothelial function in hypercholesterolemic rabbits. Int J Mol Med. 2003;11:317–20.

    CAS  PubMed  Google Scholar 

  12. Mizutani K, Ikeda K, Kawai Y, Yamori Y. Resveratrol attenuates ovariectomy-induced hypertension and bone loss in stroke-prone spontaneously hypertensive rats. J Nutr Sci Vitaminol. 2000;46:78–83.

    CAS  PubMed  Google Scholar 

  13. Rush JWE, Quadrilatero J, Levy AS, Ford RJ. Chronic resveratrol enhances endothelium-dependent relaxation but does not alter eNOS levels in aorta of spontaneously hypertensive rats. Exp Biol Med. 2007;232:814–22.

    CAS  Google Scholar 

  14. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending lifespan. Cell Metab. 2008;8:157–68.

    Article  CAS  PubMed  Google Scholar 

  15. Kauser K, Rubanyi GM. Gender difference in bioassayable endothelium-derived nitric oxide from isolated rat aortae. Am J Physiol Heart Circ Physiol. 1994;267:H2311–7.

    CAS  Google Scholar 

  16. Nickenig G, Baumer AT, Grohe C, Kahlert S, Strehlow K, Rosenkranz S, et al. Estrogen modulates AT1 receptor gene expression in vitro and in vivo. Circulation. 1998;97:2197–201.

    CAS  PubMed  Google Scholar 

  17. Crews JK, Murphy JG, Khalil RA. Gender differences in Ca2+ entry mechanisms of vasoconstriction in Wistar-Kyoto and spontaneously hypertensive rats. Hypertension. 1999;34:931–6.

    CAS  PubMed  Google Scholar 

  18. Walsh T, Donnelly T, Lyons D. Impaired endothelial nitric oxide bioavailability: a common link between aging, hypertension, and atherogenesis? J Am Geriat Soc. 2009;57:140–5.

    Article  PubMed  Google Scholar 

  19. Skatchkov MP, Sperling D, Hink U, Mulsch A, Harrison DG, Sindermann I. Validation of lucigenin as a chemiluminescent probe to monitor vascular superoxide as well as basal vascular nitric oxide production. Biochem Biophys Res Commun. 1999;254:319–24.

    Article  CAS  PubMed  Google Scholar 

  20. Coskun B, Soylemez S, Parlar AI, Ulus AT, Katircioglu SF, Akar F. Effect of resveratrol on nitrate tolerance in isolated human internal mammary artery. J Cardiovas Pharmacol. 2006;47:437–45.

    CAS  Google Scholar 

  21. Chambliss KL, Shaul PW. Estrogen modulation of endothelial nitric oxide synthase. Endoc Rev. 2002;23:665–86.

    Article  CAS  Google Scholar 

  22. Andersen HL, Weis JU, Fjalland B, Korsgaard N. Effect of acute and long-term treatment with 17-β-estradiol on the vasomotor responses in the rat aorta. Br J Pharmacol. 1999;126:159–68.

    Article  CAS  PubMed  Google Scholar 

  23. Gonzales RJ, Walker BR, Kanagy NL. 17β-Estradiol increases nitric oxide-dependent dilation in rat pulmonary arteries and thoracic aorta. Am J Physiol Lung Cell Mol Physiol. 2001;280:L555–64.

    CAS  PubMed  Google Scholar 

  24. Sobey CG, Weiler JM, Boujaoude M, Woodman OL. Effect of short-term phytoestrogen treatment in male rats on nitric oxide-mediated responses of carotid and cerebral arteries: comparison with 17 β-estradiol. J Pharmacol Exp Therap. 2004;310:135–40.

    Article  CAS  Google Scholar 

  25. Gehm BD, McAndrews JM, Chien PY, Jameson JL. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Nat Acad Sci USA. 1997;94:14138–43.

    Article  CAS  PubMed  Google Scholar 

  26. Lu R, Serrero G. Resveratrol, a natural product derived from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells. J Cell Physiol. 1999;179:297–304.

    Article  CAS  PubMed  Google Scholar 

  27. Miyazaki R, Ichiki T, Hashimoto T, Inanaga K, Imayama I, Sadoshima J, et al. SIRT1, a longevity gene, downregulates angiotensin II type 1 receptor expression in vascular smooth muscle cells. Arterioscler Throm Vasc Biol. 2008;28:1263–9.

    Article  CAS  Google Scholar 

  28. Aubin M-C, Lajoie C, Clement R, Gosselin H, Calderone A, Perrault LP. Female rats fed a high-fat diet were associated with vascular dysfunction and cardiac fibrosis in the absence of overt obesity and hyperlipidemia: therapeutic potential of resveratrol. J Pharmacol Exp Therap. 2008;325:961–8.

    Article  CAS  Google Scholar 

  29. Bradamante S, Barenghi L, Villa A. Cardiovascular protective effects of resveratrol. Cardiovas Drug Rev. 2004;22:169–88.

    CAS  Google Scholar 

  30. Mueller CFH, Laude K, McNally JS, Harrison DG. Redox mechanisms in blood vessels. Arterioscler Throm Vasc Biol. 2005;25:274–8.

    Article  CAS  Google Scholar 

  31. Guzik TJ, West NE, Black E, McDonald D, Ratnatunga C, Pillai R, et al. Vascular superoxide production by NAD(P)H oxidase: association with endothelial dysfunction and clinical risk factors. Circ Res. 2000;86:85–90.

    Google Scholar 

  32. Didion SP, Faraci FM. Effects of NADH and NADPH on superoxide levels and cerebral vascular tone. Am J Physiol Heart Circ Physiol. 2002;282:H688–95.

    CAS  PubMed  Google Scholar 

  33. Ungvari Z, Orosz Z, Rivera A, Labinskyy N, Xiangmin Z, Olson S, et al. Resveratrol increases vascular oxidative stress resistance. Am J Physiol Heart Circ Physiol. 2007;292:H2417–24.

    Article  CAS  PubMed  Google Scholar 

  34. Griendling KK, FitzGerald GA. Oxidative stress and cardiovascular injury, part II: animal and human studies. Circulation. 2003;108:2034–40.

    Article  PubMed  Google Scholar 

  35. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Disc. 2006;5:493–506.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from the Gazi University Research Fund (BAP 02/2005-21 and 02/2006-11).

Conflict of interest

The authors state no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey

    Selen Soylemez & Fatma Akar

  2. Department of Medical Biochemistry, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey

    Aylin Sepici

  3. Gazi Universitesi, Eczacılık Fakültesi, Farmakoloji Anabilim Dalı, 06330, Etiler, Ankara, Turkey

    Fatma Akar

Authors
  1. Selen Soylemez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aylin Sepici
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fatma Akar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fatma Akar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Soylemez, S., Sepici, A. & Akar, F. Resveratrol Supplementation Gender Independently Improves Endothelial Reactivity and Suppresses Superoxide Production in Healthy Rats. Cardiovasc Drugs Ther 23, 449–458 (2009). https://doi.org/10.1007/s10557-009-6198-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-009-6198-z

Key words

Search

Navigation